Synthesis Of Vitamin E Succinate And The Research Of Its Self-emulsifying Drug Delivery System

The drug, Vitamin E Succinate(VES) was studied in this work. The research covered synthetic technology , quantitative analytical methods, physicochemical properties and chemical stability. Developed and characterized self-emulsifying drug delivery systems (SEDDS), Optimized formulation, and studied pharmacokinetics in rabbit .With d,l-a-tocopherol and succinic anhydride as the materials, pyriodine as the solvent, VES was prepared. Using molar ratio of d,l-a-tocopherol and succinic anhydride, amount of solvent, reaction temperature and reaction time as the test factors, chosing three levels and taking the reaction yield as the test criterion, synthesis process of VES was optimized by applying orthogonal design. It was found that the optimum process was molar ratio 1:5, solvent volume 10ml(the total weight of d,l-a-tocopherol and succinic anhydride was 3 grams), reaction temperature 90 C and reaction time 5 h. The average yield of the products was 97.16% according to the repeated experiments.High-performation liquid chromatography with UV detection was developed for in vivo assay during the studies of physiochemical properties , content , release as well as in situ absorption .In the preformation researchs the physico-chemical properties of VES were investigated , which were connected closely with pharmaceutical form design .The studies showed the solubility of VES that in distilled water, 0.1M HC1, 0.1MNaOH were 0.081mg/ml, 0.047mg/ml, 0.313mg/ml . Apperant oil-water partition coefficient in different environment were samilar. In addition , the chemical stability of VES was observed , the result of which indicated that temperature , moisture and oxygen had much effect on it.Developed and characterized SEDDS of VES, SEDDS formulations were prepared using different oils, surfactants and cosurfactants. In all the formulations, the level of VES was fixed at 10%(w/w) of the vehicles. Pseudo-ternary phase diagrams was constructed identifying the efficient self-emulsification region. The in vitro self-emulsification properties and release of VES were studied. From these studies, an optimized formulation consisting of 40%tween80, 10%PEG400, 40%oleate ethyl, 10%VES was selected, its bioavailability and a formulation using vegetable oil as vehicle were compared in rabbit. A 1.54 fold increase in the bioavailability was observed for the self-emulsifying system compared to a formulation using only vegetable oil as vehicle. SEDDS has improved the bioavailability of VES significantly. The date suggest the potential use of SEDDS to provide an efficient way of improving oral absorption of lipophilic drugs.